Extracellular Matrix In Tumor Biology

This volume provides an overview on the influence of Extracellular Matrix (ECM) on tumor progression. It covers topics such as signaling induced by structural ECM proteins including collagen and fibronectin, the control of ECM deposition and the turnover in tumors. Also discussed are the migration of cells through basement membranes and the function of proteoglycans including lumican and veriscan in tumor progression. Biomaterial-based in-vitro models as well as C. elegans models of the tumor microenvironment are used to show how these models can lead to a greater understanding of the disease mechanisms that promote cancer progression. The book addresses researchers working on cancer biology or ECM, and oncologists alike.

This book introduces the most important and best studied extracellular and pericellular molecules of the tumor microenvironment. It gives a comprehensive overview of their role in tumor development and cancer progression. Twelve chapters deal with the biochemical and biophysical background of extracellular matrix (ECM) changes in the tumor stroma compared to the physiological state. The reader learns about the major ECM components that are deregulated during cancer development and how they are associated with cancer progression associated with survival, inflammation process, among others. These are followed by recent data about the cooperative activity of extracellular matrix in tumor metabolism, promoting cancer progression. Two chapters focus specifically on the critical role of the ECM in tumor angiogenesis, linking this process to cellular infiltration and metastatic behavior of tumors. The final part describes how the ECM influences the success of immuno- and chemotherapy in cancer patients, its potential as biomarkers for diagnosis, prognosis, and therapeutic target, as well as the mechanism of resistance-associated changes in the ECM. This book is an interesting read for anyone who want to know more about ECM and cancer biology. Early career scientists can use it as an introduction to the field, offering an excellent tool for studying ECM. Advanced researchers and clinicians can gain a broader overview of the subject, considering the role of ECM for influencing every cancer hallmark as well as in the response of cancer treatments. The work serves to inspire future research and shows that the ECM should be considered as an important factor in the development of cancer therapeutics. The series "Biology of Extracellular Matrix" is published in collaboration with the American Society for Matrix Biology and the International Society for Matrix Biology.

Cancer was thought to originate from alterations in intercellular signaling that resulted in the transformation of cells, their uncontrolled proliferation and metastasis. There is now an increasing body of evidence demonstrating that the surrounding matrix and cell-matrix interactions are also major players in this process. Cells adhere and receive signals from various extracellular matrices via transmembrane receptors, the best known of which are the heterodimeric glycoproteins, integrins.

Over the last decades cell biology and biological chemistry have increasingly turned their attention to the space between cells and revealed an elaborate network of macromolecules essential for structural support, cell adhesion and signaling. This comprehensive handbook of the extracellular matrix will give an overview of the current state of knowledge of matrix components (structure and function), their role in heath and disease (matrix pathobiology) and new aspects related to pharmacological targeting. It will provide an introduction to the extracellular matrix and detailed sections and chapters on: Importance of extracellular matrix in health and disease Matrix proteoglycans (aggrecan, versican, perlecan, SLRPs, syndecans, glypicans, serglycin) Matrix proteinases (remodeling, would healing, regulatory roles in health and disease, metalloproteinases, cystein proteases, plasmin and plasminogen activator system) Glycobiology (hyaluronan and sulfated glycosaminoglycans in cancer, inflammation and metabolic control) Collagens (supramolecular assembly, proteins binding collagen, scaffolds, bacterial and mutated collagens, procollagen proteinases) Cell surface receptors (integrins, syndecans, mechanical strain and TGFb, CD44 and DDR). Biotechnological and pharmacological outlook (matrix regulation by growth factors, hyaluronidases, pathobiology, disease targeting, delivery systems, EMT and proteomics). "The book Extracellular Matrix: Pathobiology and Signaling provides a comprehensive and up to date collection of very relevant topics for understanding the various facets of extracellular matrix and its interactions with cells in normal tissue as well as in disease. It represents the current front-line and will serve as a reference for extracellular matrix and posttranslational modifications." Dick Heinegård, Department of Clinical Sciences Lund, Section Rheumatology, Lund University, Sweden

Knowledge of the extracellular matrix (ECM) is essential to understand cellular differentiation, tissue development, and tissue remodeling. This volume of the series “Biology of Extracellular Matrix” provides a timely overview of the structure, regulation, and function of the major macromolecules that make up the extracellular matrix. It covers topics such as collagen types and assembly of collagen-containing suprastructures, basement membrane, fibronectin and other cell-adhesive glycoproteins, proteoglycans, microfibrils, elastin, fibulins and matricellular proteins, such as thrombospondin. It also explores the concept that ECM components together with their cell surface receptors can be viewed as intricate nano-devices that allow cells to physically organize their 3-D-environment. Further, the role of the ECM in human disease and pathogenesis is discussed as well as the use of model organisms in elucidating ECM function.

This book would like to present the latest findings on different aspects of tumor matrix formation in connection with the tumor progression and metastasis and on alterations in the cellular components of tumor stroma during tumor demarcation and invasion.

In the ten-year interval since the first edition of this volume went to press, our knowledge of extracellular matrix (ECM) function and structure has enor mously increased. Extracellular matrix and cell-matrix interaction are now routine topics in the meetings and annual reviews sponsored by cell biology societies. Research in molecular biology has so advanced the number of known matrix molecules and the topic of gene structure and regulation that we won dered how best to incorporate the new material. For example, we deliberated over the inclusion of chapters on molecular genetics. We decided that with judicious editing we could present the recent findings in molecular biology within the same cell biology framework that was used for the first edition, using three broad headings: what is extracellular matrix, how is it made, and what does it do for cells? Maintaining control over the review of literature on the subject of ECM was not always an easy task, but we felt it was essential to production of a highly readable volume, one compact enough to serve the the student as an introduction and the investigator as a quick update on graduate the important recent discoveries. The first edition of this volume enjoyed con hope the reader finds this edition equally useful. siderable success; we D. Hay Elizabeth vii Contents Introductory Remarks 1 Elizabeth D. Hay PART I. WHAT IS EXTRACELLULAR MATRIX? Chapter 1 Collagen T. F. Linsenmayer 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 2. The Collagen Molecule . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2. 1. Triple-Helical Domain(s) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .